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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2008-2-18
pubmed:abstractText
Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) can promote functional recovery of brain after stroke with the mechanism regulating the BMSCs migration to ischemic penumbra poorly understood. Interaction between stromal cell-derived factor-1alpha (SDF-1alpha) and its cognate receptor CXCR4 is crucial for homing and migration of multiple stem cell types. Their potential role in mediating BMSC migration in ischemic brain has not been demonstrated. In this study, ischemic brain lesion model was created in rats by permanent middle cerebral artery occlusion and green fluorescent protein (GFP)-labeled BMSCs were intravenously injected. Immunohistochemical staining showed that BMSCs were able to enter the route from olfactory areas to cortex of the rat brain. Significant recovery of modified Neurological Severity Score was observed at days 14 and 28. Interestingly, the SDF-1alpha mRNA and protein were predominantly localized in the ischemic penumbral, peaked by 3-7 days and retained at least 14 days post-transplantation. On the other hand, the CXCR4 expression by BMSCs was elevated under hypoxia. The pre-treatment with the CXCR4-specific antagonist AMD3100 significantly prevented the migration of BMSCs to the injured brain. Taken together, these observations indicate that systemically administered BMSCs can migrate to the ischemic lesion of brain along with the olfactory-thalamus and hippocampus-cortex route. The interaction of locally produced SDF-1alpha and CXCR4 expressed on the BMSC surface plays an important role in the migration of transplanted cells, suggesting that it might be a potential approach to modulate the expression of the two molecules in order to further facilitate the therapeutic effects using BMSCs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0006-8993
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
1195
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
104-12
pubmed:meshHeading
pubmed-meshheading:18206136-Animals, pubmed-meshheading:18206136-Bone Marrow Cells, pubmed-meshheading:18206136-Bone Marrow Transplantation, pubmed-meshheading:18206136-Brain Ischemia, pubmed-meshheading:18206136-Cell Movement, pubmed-meshheading:18206136-Cerebral Cortex, pubmed-meshheading:18206136-Chemokine CXCL12, pubmed-meshheading:18206136-Disease Models, Animal, pubmed-meshheading:18206136-Gene Expression Regulation, pubmed-meshheading:18206136-Hippocampus, pubmed-meshheading:18206136-Immunohistochemistry, pubmed-meshheading:18206136-Male, pubmed-meshheading:18206136-RNA, Messenger, pubmed-meshheading:18206136-Rats, pubmed-meshheading:18206136-Rats, Sprague-Dawley, pubmed-meshheading:18206136-Receptors, CXCR4, pubmed-meshheading:18206136-Stem Cell Transplantation, pubmed-meshheading:18206136-Stromal Cells
pubmed:year
2008
pubmed:articleTitle
SDF-1alpha/CXCR4-mediated migration of systemically transplanted bone marrow stromal cells towards ischemic brain lesion in a rat model.
pubmed:affiliation
Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Er Lu, 510080, Guangzhou, PR China.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't